Catalytic Cyclization Research Articles

Evaluation of the Catalytic Ability of Sulfocationites Based on Petroleum Asphaltenes in the Synthesis of Pyrazolidin-3-one

The feasibility of the room temperature catalytic cyclization of hydrazine hydrate and acrylic acid in the presence of an acidic catalyst containing petroleum asphaltenes was explored. The effect of sulfocationite on the synthesis of the target pyrazolidin-3-one was studied. Reaction masses and their distillation residues were analyzed. Gas chromatography–mass spectrometry and electrospray ionization were used to reveal different individual, oligomeric and polymeric products. The most probable structures of the obtained products were proposed.

SYNTHETIC APPROACHES TO HYDROGENIZED PYRIDYL[b]AZEPINE AND THEIR BENZENELYLATED ANALOGUES

Pyrido[b]azepines are represented in the literature by four types of isomeric structures: pyrido[3,2-b] azepines, pyrido[2,3-b]azepines, pyrido[3,4-b] azepines and pyrido[4,3-b ]azepines. They belong to the structural analogues of 1-benzazepine - an attractive class of heterocycles with a strong pharmacological profile. They are also used as important molecular platforms in the construction of bioactive compounds. Analysis of the literature has shown that compounds that contain the pyrido[b]azepine fragment demonstrate antiviral, antimicrobial, and antitumor activity. They are knownas effective inhibitors of R1P1 kinase, ubiquitin- specific proteases (USPS), cyclin-dependent kinase (CDKS), and glycogen synthase kinase 3 (GSK-3), TRPM8 protein, and angiotensin I type 2 (AT2) receptors. Over the last decade, promising pharmacological properties of pyrido[b]azepine derivatives stimulated the development of fundamentally new methods of their synthesis as well as the improvement of known synthetic approaches. In general, among the various methods for the synthesis of hydrogenated pyrido[b] azepines and their benzanelated analogues, priority is currently given to approaches that include the formation of an azepine cycle via the intermolecular formation of C-N and C-C bonds. These mainly include catalytic cyclizations using cobalt, palladium, and rhodium compounds. Reactions of intramolecular radical difluoromethylarylation and diauryl peroxide-initiated radical azepine analelenization of the pyridine fragment are also of great importance. An interesting method for the synthesis of pyrido [2,3-b] azepin-5-one derivatives was developed on the basis of the Friedel-Crafts intramolecular cycloalkylations reaction.

Synthesis Cu(I)–CN-based MOF with in-situ generated cyanogroup by cleavage of acetonitrile: Highly efficient for catalytic cyclization of propargylic alcohols with CO2

Developing a highly effective process for synthesis a cyano-bridged compound to avoid toxic organic or inorganic cyanides is very significant method for alleviating cyanides pollution. Here, a CN-based MOF catalyst (Cu(I)–CN–BPY) was synthesized by using copper ions coupled with Na4W10O32 in CH3CN under solvothermal conditions. The cyano-groups are generated in situ from the cleavage of C(sp3)–C(sp) in CH3CN. Because Cu(I) sites have ability to activate π-activate internal alkynes of carbon–carbon triple bonds for carboxylic cyclization reactions, which was applied in the cyclization of propargylic alcohols with CO2 and exhibited high efficiency with >95 % yields. For seeking out the active sites of MOF structure in carboxylic cyclization, we also synthesized two MOFs of Cu(I)–Cl–BPY and Cu(I)–I–BPY, and investigated for this reaction.

Facile Synthesis of Aryl-Substituted Cycloarenes via Bismuth(III) Triflate-Catalyzed Cyclization of Vinyl Ethers

Cycloarenes are an essential class of polycyclic aromatic hydrocarbons with unique electronic structure, but their synthesis is very challenging. Herein, we report a facile synthetic strategy prima...

New Twists in Nazarov Cyclization Chemistry.

The defining feature of the Nazarov cyclization is a 4π-conrotatory electrocyclization, resulting in the stereospecific formation of functionalized cyclopentanones. The reaction provides access to structural motifs that are found in many natural products and drug targets. Harnessing the full potential of the Nazarov cyclization broadens its utility by enabling the development of new methodologies and synthetic strategies. To achieve these goals through efficient cyclization design, it is helpful to think of the reaction as a two-stage process. The first stage involves a 4π-electrocyclization leading to the formation of an allylic cation, and the second stage corresponds to the fate of this cationic intermediate. With a complete understanding of the discrete events that characterize the overall process, one can optimize reactivity and control the selectivity of the different Stage 2 pathways.In this Account, we describe the development of methods that render the Nazarov cyclization catalytic and chemoselective, focusing specifically on advances made in our lab between 2002 and 2015. The initial discovery made in our lab involved reactions of electronically asymmetric ("polarized") substrates, which cyclize efficiently in the catalytic regime using mild Lewis acidic reagents. These cyclizations also exhibit selective eliminative behavior, increasing their synthetic utility. Research directed toward catalytic asymmetric Nazarov cyclization led to the serendipitous discovery of a 4π-cyclization coupled to a well-behaved Wagner-Meerwein rearrangement, representing an underexplored Stage 2 process. With careful choice of promoter and loading, it is possible to access either the rearrangement or the elimination pathway. Additional experimental and computational studies provided an effective model for anticipating the migratory behavior of substiutents in the rearrangements. Problem-solving efforts prompted investigation of alternative methods for generating pentadienyl cation intermediates, including oxidation of allenol ethers and addition of nucleophiles to dienyl diketones. These Nazarov cyclization variants afford cyclopentenone products with vicinal stereogenic centers and a different arrangement of substituents around the ring. A nucleophilic addition/cyclization/elimination sequence can be executed enantioselectively using catalytic amounts of a nonracemic chiral tertiary amine.In summary, the discovery and development of several new variations on the Nazarov electrocyclization are described, along with synthetic applications. This work illustrates how strongly substitution patterns can impact the efficiency of the 4π-electrocyclization (Stage 1), allowing for mild Lewis acid catalysis. Over the course of these studies, we have also identified new ways to access the critical pentadienyl cation intermediates and demonstrated strategies that exploit and control the different cationic pathways available post-electrocyclization (Stage 2 processes). These advances in Nazarov chemistry were subsequently employed in the synthesis of natural product targets such as (±)-merrilactone A, (±)-rocaglamide, and (±)-enokipodin B.

Mechanistic investigations on C–H activated dealkylating cyclo-amination reactions of substituted triazenes, formamidines and amidines

Abstract Catalytic dealkylating cycloamination reactions of N 1-methylated-N 1,N 3-diarylated triazenes proceed via two subsequent oxidative addition reactions, regioselectivity producing benzotriazoles by C–H and C–Br activation steps. Whereas palladium-based catalysis in the presence of dealkylating reagents and directing phosphane ligands leads to high yields, the homologous metals nickel and platinum as well as other 3d transition metals show only poor catalytic activity in similar procedures. Starting compounds have been widely varied to introduce potentially competing reaction sites and to investigate the reaction mechanism of the catalytic cyclization reactions. Yields of the benzotriazole synthesis strongly depend on the electronic and steric properties of the directing phosphane ligands, the nature of the dealkylating bases and the substitution pattern in 2- and 4-position of the aryl groups of the starting triazenes. In order to clarify the role of the catalyst, palladium-based intermediates were identified. Finally, formamidines and bulky amidines were tested in related C–H activated dealkylating cycloamination reactions.

Microwave-assisted acid-induced formation of linker vacancies within Zr-based metal organic frameworks with enhanced heterogeneous catalysis

Herein, we report a microwave-assisted acid-induced post-treatment method for the formation of linker vacancies within Zr-based metal organic frameworks (Zr-MOFs). The number of linker vacancies can be easily regulated with this method by changing the concentration of the HCl solution and the duration of microwave irradiation. The optimized defective UiO-66 showed higher linker defects with a higher specific surface area and thermal stability. The results of the catalytic cyclization of citronella showed that the Zr-MOFs with more defects exhibited enhanced catalytic performance. This work may provide a new method for the creation of defective MOFs with high activity and stability.

Ytterbium-Catalyzed Intramolecular [3 + 2] Cycloaddition based on Furan Dearomatization to Construct Fused Triazoles.

The 1,2,3-triazole-containing polycyclic architecture widely exists in a broad spectrum of synthetic bioactive molecules, and the development of expeditious methods to synthesize these skeletons remains a challenging task. In this work, the catalytic cyclization of biomass-derived 2-furylcarbinols with an azide to form fused triazoles is described. This approach takes advantage of a single catalyst Yb(OTf)3 and operates via a furfuryl-cation-induced intramolecular [3 + 2] cycloaddition/furan ring-opening cascade.

Facile Synthesis of 2‐Amino‐4,6‐dimethoxypyrimidine over Lewis Acidic Ionic Liquid Catalysts

Abstract2‐amino‐4,6‐dimethoxypyrimidine (ADMP) is an important intermediate for the synthesis of sulfonylurea herbicides. As the most critical step in the ADMP synthesis, ADMP prepared by cyclization of 3‐amino‐3‐methoxy‐N‐cyano‐2‐propaneamidine (AMCP) are rarely reported, especially its reaction mechanism. Here, a Lewis acidic ionic liquid catalyst was firstly introduced to increase reaction rate. The Et3NHCl‐2ZnCl2 catalyst possesses excellent catalytic performance and good stability. The yield of ADMP can reach up to 94.8% under 50 °C for 3 h. And the catalytic mechanism was studied. The anion of Et3NHCl‐2ZnCl2 is conducive to ring formation, and the cation is conducive to hydrogen transfer during rearrangement. The stronger Lewis acidity of the catalyst is conducive to cyclization. This work firstly introduces Lewis acidic ionic liquids into the process of AMCP catalytic cyclization to ADMP, which can open novel vistas for the more economically and faster preparation for ADMP.

A Structural View on the Maturation of Lanthipeptides.

Lanthipeptides are ribosomally synthesized and posttranslationally modified peptides, which display diverse bioactivities (e.g., antifungal, antimicrobial, and antiviral). One characteristic of these lanthipeptides is the presence of thioether bonds, which are termed (methyl-) lanthionine rings. These modifications are installed by corresponding modification enzymes in a two-step modality. First, serine and threonine residues are dehydrated followed by a subsequent catalyzed cyclization reaction, in which the dehydrated serine and threonine residues are undergoing a Michael-type addition with cysteine residues. The dedicated enzymes are encoded by one or two genes and the classification of lanthipeptides is pending on this. The modification steps form the basis of distinguishing the different classes of lanthipeptides and furthermore reflect also important mechanistic differences. Here, we will summarize recent insights into the mechanisms and the structures of the participating enzymes, focusing on the two core modification steps – dehydration and cyclization.

Cover Picture

The cover picture shows that a new class of axially chiral aryl‐alkene‐indole frameworks has been constructed by the strategy of designing 3‐alkynyl‐2‐indolylmethanols as versatile reactants for catalytic asymmetric cyclizations. This approach represents the first catalytic asymmetric construction of axially chiral alkene‐heteroaryl scaffolds, which will add a nascent member to the atropisomeric family. The authors devised the innovative strategy to construct the intriguing axially chiral frameworks, just like Nuwa used the 'five‐colored stone' to mend the sky in the mythology of ancient China. More details are discussed in the article by Shi and Jiao et al. on page 543—552.image

Axially Chiral 1,1'‐Binaphthyl‐2‐Carboxylic Acid (BINA‐Cox) as Ligands for Titanium‐Catalyzed Asymmetric Hydroalkoxylation

Axially chiral, enantiopure 1,1'‐binaphthyl‐2‐carboxylic acids (BINA‐Cox) have recently been introduced as chiral ligands for transition metal catalysis. Together with equimolar, co‐catalytic amounts of Ti(OiPr)4 and water they form an in situ catalyst that performs the asymmetric catalytic hydroalkoxylation of 2‐allylphenols to 2‐methylcoumarans at high temperature (240 °C, microwave heating). The synthesis of reference ligand 2'‐MeO‐BINA‐Cox (L1) has been optimized and performed at molar scale. Synthetic routes have been developed to access a variety of substituted BINA‐Cox ligands (>30 examples), which have been tested for ligand effects on the reference asymmetric cyclization of 2‐allylphenol. The substrate range of asymmetric catalytic hydroalkoxylation has been explored through systematic substrate structure variations to define scope and limitations of the titanium‐catalyzed process. The new substrates 2‐(1‐vinylcycloalkyl)phenols (1j, 1k), 2‐(2‐vinylphenyl)propan‐2‐ol (1t), and 2'‐vinyl‐[1,1'‐biphenyl]‐2‐ol (1u) are shown to undergo asymmetric catalytic cyclization to benzodihydrofurans and benzo[c]chromene, respectively.

Enantioselective Dearomative Cyclization of Homotryptamines with Allenamides into Indolo[2,3‐b]quinolines

AbstractWe have developed a catalytic asymmetric dearomative cyclization of homotryptamine derivatives, furnishing enantioenriched indolo[2,3‐b]quinoline scaffolds. The activation of allenamides in the presence of chiral phosphoric acids triggered the dearomative cyclization in up to 99% ee.magnified image

Catalytic Direct Cyclization of Alkenyl Thioester

Herein we report a one-step, catalytic, Markovnikov-selective, and scalable method for the synthesis of saturated sulfur heterocycles, which are found in the structures of pharmaceuticals and natur...

Copper (II) as catalyst for intramolecular cyclization and oxidation of (1,4-phenylene)bisguanidines to benzodiimidazole-diylidenes

A synthetically useful approach of catalytic intramolecular cyclization and oxidation of 2′,2′-(1,4-phenylene)bis(1,3-dialkyl)guanidines (Alkyl = isopropyl 1 or cyclohexyl 2) catalyzed by copper acetate in acetonitrile under air was studied by on line monitoring of the reaction by ESI-MS. All-important intermediates organic species were intercepted during the experiment confirming for the first time the stepwise (1,4-phenylene)bisguanidines cyclization and oxidation mechanism. Moreover, performed collision-induced dissociation (CID) experiments were also applied as a structure elucidation tool. Bimetallic copper intermediates Cu1 ([C28H48Cu2N6O10 + H]+) of m/z 755 and Cu2 [C22H36Cu2N6O4 + H]+ of m/z 575 were documented. The plausible key mechanistic steps involving the formation of organic and inorganic intermediates detected by in situ monitoring of the reaction are presented.

A sulfur-containing hetero-octulene: synthesis, host–guest properties, and transistor applications

A heterocycloarene derivative (S-Octulene) possessing two sulfur atoms was conveniently synthesized through Bi(OTf)3-catalyzed cyclization from a macrocyclic tetramethoxyethenylated precursor. The physical properties of S-Octulene and its supramolecular host-guest interaction with C60 and C70 were investigated by fluorescence titration and 1H NMR. The solution-processed organic field-effect transistor (OFET) measurements demonstrated that S-Octulene behaved as a p-type semiconductor with a hole mobility exceeding 0.01 cm2 V-1 s-1. Our findings pave a new path to design novel heterocycloarenes for the development of host-guest chemistry and organic semiconductors.

Catalytic enantioselective arylative cyclizations of alkynyl 1,3-diketones by 1,4-rhodium(i) migration.

The enantioselective synthesis of densely functionalized polycarbocycles by the rhodium(i)-catalyzed reaction of arylboronic acids with 1,3-diketones is described. The key step in these desymmetrizing domino addition–cyclization reactions is an alkenyl-to-aryl 1,4-Rh(i) migration, which enables arylboronic acids to function effectively as 1,2-dimetalloarene surrogates.

Asymmetric catalysis with a chiral-at-osmium complex.

The first example of a chiral osmium catalyst is reported in which the overall chirality originates exclusively from a stereogenic metal center (metal-centered chirality) with all coordinating ligands being achiral. The non-C2-symmetric chiral-at-metal complex contains two cyclometalated 7-methyl-1,7-phenanthrolinium heterocycles which can be described as two chelating pyridylidene remote N-heterocyclic carbene (rNHC) ligands. The octahedral coordination sphere is completed with one CO and one acetonitrile ligand. A monodentate chiral oxazoline ligand is used as a chiral auxiliary ligand to obtain enantiomerically pure chiral-at-osmium complexes (>99 : 1 e.r.). Finally, it is demonstrated that the developed chiral-at-osmium complex is suitable for ring-closing enantioselective C(sp3)-H aminations, including the first example of catalytic enantioselective cyclizations of azidoformates to chiral 2-oxazolidinones.

A lutidine-promoted photoredox catalytic atom-transfer radical cyclization reaction for the synthesis of 4-bromo-3,3-dialkyl-octahydro-indol-2-ones.

Reported herein is a visible-light-catalyzed photoredox atom-transfer radical cyclization (ATRC) halo-alkylation of 1,6-dienes with α-halo-ketones as the ATRC reagent. This process exhibits high atom economy, high step economy, and high redox economy, which can directly construct a 4-bromo-3,3-dialkyl-octahydro-indol-2-one core under mild conditions in one pot, and lutidine is found to be the key promoter for this ATRC process.

B(C6F5)3-Catalyzed cyclization of alkynes: direct synthesis of 3-silyl heterocyclic compounds.

An efficient one-pot strategy for easy access to 3-silyl heterocyclic compounds was developed via a B(C6F5)3-catalyzed cycloaddition reaction of o-(1-alkynyl)(thio)anisoles or o-(1-alkynyl)-N-methylaniline. In this reaction, benzenethiophene, benzofuran or indole skeletons could be constructed by an intermolecular cyclization with diphenylsilane. This protocol elicited moderate-to-good yields with metal-free reaction systems.